Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1

Xu, Yan; Zhu, Kui; Hong, Guiying; Wu, Weihua; Baudhuin, Linnea M.; Xiao, Yi; Damron, Derek S.

doi:10.1038/35010529

Cited by 273 publications

(150 citation statements)

References 46 publications

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“…All members of the OGR1 family are activated by lysophospholipids and are coupled to G␣ q or G␣ i heterotrimeric G proteins (57). It is interesting to note that several other members of the OGR1 family, including OGR1 and G2A, have been implicated as mediators of growth arrest and apoptosis (52,58). Like TDAG8, other members of the OGR1 family have only recently been paired with their ligands.…”

Section: Discussionmentioning

confidence: 99%

The Glucocorticoid-induced Gene tdag8 Encodes a Pro-apoptotic G Protein-coupled Receptor Whose Activation Promotes Glucocorticoid-induced Apoptosis

Malone

Wang

Distelhorst

2004

Journal of Biological Chemistry

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The apoptotic action of glucocorticoids on lymphocytes makes them effective therapeutics for many lymphoid malignancies. Although it is clear that glucocorticoid-induced apoptosis requires transcription, the gene products that induce apoptosis remain unknown. Using gene expression profiles of lymphoma cell lines and primary thymocytes treated with the synthetic glucocorticoid dexamethasone, we discovered that induction of tdag8 (T-cell death-associated gene 8) was a common event in each model system investigated. Activation of TDAG8 by its agonist psychosine markedly enhanced dexamethasone-induced apoptosis in a TDAG8-dependent manner. Expression of a TDAG8-GFP fusion protein was sufficient to induce apoptosis, and repression of endogenous TDAG8 using RNA interference partially inhibited dexamethasone-induced apoptosis. Together, these data suggest that TDAG8 is a regulator of glucocorticoid-induced apoptosis and that agonists of TDAG8 may be promising agents to improve the efficacy of glucocorticoids for the treatment of leukemia and lymphoma.

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Section: Discussionmentioning

confidence: 99%

The Glucocorticoid-induced Gene tdag8 Encodes a Pro-apoptotic G Protein-coupled Receptor Whose Activation Promotes Glucocorticoid-induced Apoptosis

Malone

Wang

Distelhorst

2004

Journal of Biological Chemistry

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“…On the other hand, it should be noted that the hitherto cloned receptors with high a nity for SPP all have low a nity for SPPC (Lynch & Im, 1999), and the opposite holds true for the only cloned receptor with high a nity for SPPC (Xu et al, 2000). Moreover, the a nity of SPH and GLU for either group of receptors is either low or has not been determined, and thus it remains unclear whether they can cause receptor-mediated e ects.…”

Section: Discussionmentioning

confidence: 99%

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

Bischoff

Heringdorf

Jakobs

et al. 2001

British J Pharmacology

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1 Lysosphingolipids such as sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) can act on speci®c G-protein-coupled receptors. Since SPP and SPPC cause renal vasoconstriction, we have investigated their e ects on urine and electrolyte excretion in anaesthetized rats. 2 Infusion of SPP (1 ± 30 mg kg 71 min 71 ) for up to 120 min dose-dependently but transiently (peak after 15 min, disappearance after 60 min) reduced renal blood¯ow without altering endogenous creatinine clearance. Nevertheless, infusion of SPP increased diuresis, natriuresis and calciuresis and, to a lesser extent, kaliuresis. These tubular lysosphingolipid e ects developed more slowly (maximum after 60 ± 90 min) and also abated more slowly upon lysosphingolipid washout than the renovascular e ects. 3 Infusion of SPPC, sphingosine and glucopsychosine (3 ± 30 mg kg 71 min 71 each) caused little if any alterations in renal blood¯ow but also increased diuresis, natriuresis and calciuresis and, to a lesser extent, kaliuresis. 4 Pretreatment with pertussis toxin (10 mg kg 71 3 days before the acute experiment) abolished the renovascular and tubular e ects of 30 mg kg 71 min 71 SPP. 5 These ®ndings suggest that lysosphingolipids are a hitherto unrecognized class of endogenous modulators of renal function. SPP a ects renovascular tone and tubular function via receptors coupled to G i -type G-proteins. SPPC, sphingosine and glucopsychosine mimic only the tubular e ects of SPP, and hence may act on distinct sites.

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“…In this category, we included three GPCRs that share a high degree of sequence identity with G2A: TDAG8 (14), GPR4 (15), and OGR1 (16). We also included in our analysis eight other GPCRs with specificity toward LPA and S1P, two extensively studied LPs structurally related to LPC (reviewed in ref.…”

Section: Selection Of a G2a-positive Lymphoid Cell Line For Functionamentioning

confidence: 99%

T cell chemotaxis to lysophosphatidylcholine through the G2A receptor

Radu

Yang

Riedinger

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

183

147

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G2A is an immunoregulatory G protein-coupled receptor predominantly expressed in lymphocytes and macrophages. Ectopic overexpression studies have implicated G2A as a receptor for the bioactive lysophospholipid, lysophosphatidylcholine (LPC). However, the functional consequences of LPC-G2A interaction at physiological levels of receptor expression, and in a cellular context relevant to its immunological role, remain largely unknown. Here, we show impaired chemotaxis to LPC of a T lymphoid cell line in which G2A expression was chronically down-regulated by RNA interference technology. Rescuing this phenotype by reconstitution of the physiological level of receptor expression further supports a functional connection between LPC-G2A interaction and cellular motility. Overexpression of G2A in the T lymphoid cell line significantly enhanced chemotaxis to LPC. It also modified migration toward the LPC-related molecule, lysophosphatidic acid, indicating the possibility of crosstalk between G2A and endogenous lysophosphatidic acid receptors. The role of G2A in LPCmediated cell migration may be relevant to the autoimmune syndrome associated with genetic inactivation of this G proteincoupled receptor in mice. The experimental system described here can be useful for understanding the structural requirements for LPC recognition by G2A and the signaling pathways regulated by this ligand-receptor pair.

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Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1

Cited by 273 publications

References 46 publications

The Glucocorticoid-induced Gene tdag8 Encodes a Pro-apoptotic G Protein-coupled Receptor Whose Activation Promotes Glucocorticoid-induced Apoptosis

The Glucocorticoid-induced Gene tdag8 Encodes a Pro-apoptotic G Protein-coupled Receptor Whose Activation Promotes Glucocorticoid-induced Apoptosis

Lysosphingolipid receptor‐mediated diuresis and natriuresis in anaesthetized rats

T cell chemotaxis to lysophosphatidylcholine through the G2A receptor

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